Role Of Heat Shock Protein 27 Research Articles

Protective role of heat shock protein 27 in gastric mucosal injury

Heat shock protein 27 (HSP27) mediates cytoprotective effects through its function as a molecular chaperone and through the phosphorylation-dependent stabilization of actin filaments. The role of HSP27 in gastric ulcer formation and healing is, however, unknown. The expression of HSP27 was studied in human gastric tissue specimens obtained from patients with gastric ulcers and from healthy Helicobacter pylori-negative individuals, who received low-dose aspirin, rofecoxib, and the combination in a prospective study. The susceptibility of the gastric mucosa to indomethacin-induced lesions was further studied in transgenic mice overexpressing human HSP27 (Tg(huHSP27)) and compared with wild-type mice (Wt). The expression of HSP27, COX-1, and COX-2 was investigated in Tg(huHSP27) mice and Wt mice by immunohistochemistry and western blot analysis. While no specific changes in HSP27 expression were found following exposure of healthy human gastric mucosa to oral administration of aspirin or refocoxib, chronic gastric ulcers showed strong HSP27 expression at the ulcer base and margins. Here it was expressed by granulation tissue and regenerating surface epithelium. In Tg(huHSP27) mice, overexpression of HSP27 led to a significant decrease of indomethacin-induced erosions and ulcers compared with Wt mice. COX-1 and COX-2 levels did not change. HSP27 is involved in chronic gastric ulcer repair mechanisms in humans, while overexpression of human HSP27 in gastric epithelial cells in mice reduces the susceptibility to non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration. This indicates that HSP27 expression is critical for mucosal protection in the stomach.

Heat shock protein 27 gene: Chromosomal and molecular location and relationship to Williams syndrome

Heat shock protein 27 (HSP27) is one of a number of actin-binding proteins that regulate actin polymerization. Three related HSP27 sequences had previously been mapped to chromosomes 3, 9, and X. We have used fluorescent in-situ hybridization (FISH) to correct and refine the map position of the transcribed HSP27 gene (locus HSPB1) to chromosome 7q11.23. This band also contains the site of the deletion associated with Williams syndrome (WS). To define the relationship between HSP27 and the WS deletion, we used two-color FISH on previously G-banded and photographed metaphase chromosomes from WS cell-lines and peripheral blood. Six WS patients with longer deletions that extend telomeric to the classical WS deletion region were analyzed for deletion length using HSP27, cosmids generated from P193O22 (cos11) and B350L10 (cos64 and 82), B350L10, B161A02, and B363M4. The BAC 363M4 was selected from the Washington University database and contains HSP27. Our results indicated that HSP27 was deleted in three patients and that HSP27 is telomeric to cos11, cos64, cos82, and B350L10. B363M4 was demonstrated to overlap the telomeric end of B161A02 and HSP27 may be contained partially within the telomeric end of B161A02. The possible role of HSP27 in the cognitive features of WS is discussed.

A Role for HSP27 in Sensory Neuron Survival

Peripheral nerve injury in neonatal rats results in the death of the majority of the axotomized sensory neurons by 7 d after injury. In adult animals, however, all sensory neurons survive for at least 4 months after axotomy. How sensory neurons acquire the capacity to survive axonal injury is not known. Here we describe how the expression of the small heat shock protein 27 (HSP27) is correlated with neuronal survival after axotomy in vivo and after NGF withdrawal in vitro. The number of HSP27-immunoreactive neurons in the L4 DRG is low at birth and does not change significantly for 21 d after postnatal day 0 (P0) sciatic nerve axotomy. In contrast, in the adult all axotomized neurons begin to express HSP27. One week after P0 sciatic nerve section the total number of neurons in the L4 DRG is dramatically reduced, but all surviving axotomized neurons, as identified by c-jun immunoreactivity, are immunoreactive for HSP27. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling reveals that very few HSP27-expressing neurons are dying 48 hr after neonatal axotomy. In vitro, a similar correlation exists between HSP27 expression and survival; in P0 DRG cultures, neurons that express HSP27 preferentially survive NGF withdrawal. Finally, overexpression of human HSP27 in neonatal rat sensory and sympathetic neurons significantly increases survival after NGF withdrawal, with nearly twice as many neurons surviving at 48 hr. Together these results suggest that HSP27 in sensory neurons plays a role in promoting survival after axotomy or neurotrophin withdrawal.

Early and delayed tolerance to simulated ischemia in heat-preconditioned endothelial cells: a role for HSP27.

An ischemia-mimicking metabolic stress in cultured endothelial cells from the human aorta or umbilical vein caused ATP depletion, a rise in cytosolic free Ca2+, fragmentation and aggregation of actin microfilaments, retraction of the cytoplasm, and disintegration of cell monolayer. Simultaneously, the constitutive heat shock protein 27 (HSP27) underwent dephosphorylation and formed granules inside cell nuclei. Prior heat shock (45 degreesC, 10 min) in confluent cultures conferred two phases (early and delayed) of tolerance to simulated ischemia. Although heat preconditioning did not retard the ATP drop and the free Ca2+ overload within ischemia-stressed cells, each phase of the tolerance was manifested in longer preservation of normal cell morphology during the stress. Cells exhibiting the early tolerance within 3 h after heating altered the F-actin response to ischemic stress; no microfilament debris but, instead, translocation of F-actin to the tight submembranous layer was observed. In contrast, the delayed cytoprotection preserved the preexisting F-actin bundles under simulated ischemia; this happened only after 12- to 14-h post-heat shock recovery, elevating the intracellular HSP content, and was sensitive to blockers of HSP synthesis, cycloheximide and quercetin. The dephosphorylation and intranuclear granulation of HSP27 were markedly suppressed in both phases of the heat-induced tolerance. Without heat pretreatment, similar attenuation of the HSP27 dephosphorylation/granulation and the actin cytoskeleton stability during simulated ischemia were achieved by treating cells with the protein phosphatase inhibitors cantharidin or sodium orthovanadate. We suggest that prior heat shock ameliorates the F-actin response to ischemic stress by suppressing the HSP27 dephosphorylation/granulation; this prolongs a sojourn in the cytosol of phosphorylated HSP27, which protects microfilaments from the disruption and aggregation.